The objective of this research program is to define the neurological mechanisms involved in osmoregulation of vasopressin (VP) secretion and to clarify the mechanism of action of agents used in treating clinical disorders of VP secretion. Several different aspects of osmoregulation of VP release will be assessed: 1) the nature of the final common pathway for osmotically controlled VP release will be determined utilizing an in vitro organ cultured hypothalamic-neurohypophyseal system. 2) The mechano-receptor theory of osmoreception will be investigated utilizing individual supraoptic neurons grown in a dispersed culture system. 3) The factors responsible for osmotic depression of VP production in patients with inappropriate VP secretion secondary to bronchogenic carcinoma will be analyzed using cell cultured tumor material obtained from such a patient(s). The organ cultured hypothalamic-neurohypophyseal system will be utilized to assess the direct effects on vasopressin secretion of chlorpropamide, diphenylhydantoin, and chlorpromazine, agents which are useful in the treatment of diabetes insipidus and inappropriate ADH secretion.